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Rochester Institute of Technology Rochester Institute of Technology
RIT Scholar Works RIT Scholar Works
Theses
2004
Cyclic Olefin Copolymer (COC) in the pharmaceutical industry Cyclic Olefin Copolymer (COC) in the pharmaceutical industry
Amgad Khalil
Follow this and additional works at: https://scholarworks.rit.edu/theses
Recommended Citation Recommended Citation Khalil, Amgad, "Cyclic Olefin Copolymer (COC) in the pharmaceutical industry" (2004). Thesis. Rochester Institute of Technology. Accessed from
This Thesis is brought to you for free and open access by RIT Scholar Works. It has been accepted for inclusion in Theses by an authorized administrator of RIT Scholar Works. For more information, please contact [email protected].
Cyclic Olefin Copolymer (COC) in the Pharmaceutical Industry
by
Amgad Khalil
A Thesis Project
Submitted to the
Department of Packaging Science
College ofApplied Science and Technology
In partial fulfillment of the requirements for the degree of
Master of Science
Rochester Institute of Technology
2004
11
Department of Packaging Science College of Applied Science and Technology
Rochester Institute of Technology Rochester, New York
CERTIFICATE OF APPRO V AL
M. S. DEGREE THESIS PROJECT
The M.S. degree thesis project of Amgad Khalil has been examined and approved
by the thesis committee as satisfactory for the requirements for the Master of Science Degree
Deanna M. Jacobs
Deanna M. Jacobs RIT, Packaging Science Graduate Program Chair
III
Craig E. Densmore
Craig E. Densmore RIT, Packaging Science Professor and
Agrilink Director Packaging Procurement
Daniel L. Goodwin
Daniel L. Goodwin, PhD RIT, Packaging Science Professor
August 2004
COPY RELEASE
Permission From Author Required
CYCLIC OLEFIN COPOLYMER (COC) IN THE PHARMACEUTICAL INDUSTRY
I, Amgad Khalil, prefer to be contacted eac h lime a req uest for reproduction is made. If permission is granted, any reproduction will not be for commercia l use or profit. I can be reached at the fo llowing address:
Amgad Khalil
Date: March 21, 2005 Signature of Author: Am gad Kh a Ii I
IV
ACKNOWLEDGEMENTS
I would like to thank my advisors- DeannaM. Jacobs, Craig E. Densmore and Dr. Daniel L.
Goodwin from Rochester Institute ofTechnology- for their guidance and support.
DEDICATION
I dedicate this thesis to my wife Suzy, my son Jeremy, and my daughter Justine, as well asto my
brother Aiman and mother Alice. It is their love and support that helped me navigate through my
educational journey.
My wife's unending belief in me and unmatched sacrifice; my children's love, hugs, and kisses;
my brother as a role model; and my mother's encouragement are whatkept me going.
vi
ABSTRACT
The purpose of this research was to evaluate an alternative to polyvinyl chloride based
packaging materials for pharmaceutical blister packaging that is neither harmful to the
environment nor corrosive to the equipment used in pharmaceutical packaging. Olefin structures
(PP/COC/PP) were tested and compared to halogen based material (PVC/PVDC) using the
following criteria:
Moisture Vapor Transmission Rate (MVTR)
Vacuum leak test
Peel strength test
Machine ability and form-ability on an Uhlmann UPS4 thermoformer
Layer distribution
Financial impact
Cyclic Olefin Copolymers (COC) was proven to have the properties required to
adequately protect the product while being environmentally safer than PVDC and CTFE.
vn
TABLE OF CONTENTS
BACKGROUND 1
PVC (POLYVINYL CHLORIDE, VINYL) 3
PVC Toxicity 5
Transport Nightmare 7
Packaging ShelfLife 8
Is PVC Recyclable? 8
PVC Disposal 9
PVC Illusion 11
Victims of the PVC Industry 12
AN ALTERNATIVE TO PVC FOR PHARMACEUTICAL PACKAGING 14
COC (OLEFIN POLYMER) 15
Development and Structure ofCOC 15
Manufacturing ofCOC 15
COC in Flexible Films 16
Environmentally SafeBlister Packagingwith ImprovedBarrier Properties 17
Processing 18
Properties of COC 18
PharmaceuticalBlister PackagingRequirements 19
TEST RESULTS 20
MVTR 21
VacuumLeakTest 30
Peal StrengthTest 31
OpticalLayerGauge 33
Price Comparison 37
CONCLUSION 38
CONSIDERATIONS 39
REFERENCES 40
APPENDIX A: DEFINITIONS 42
vm
LIST OF FIGURES
Figure 1. Uhlmann Thermoformer, Model # UPS4 MT (Pfizer Parsippany Plant) 22
Figure 2. MVTR Data Graph 29
Figure 3. Blister Vacuum Leak Tester (Pfizer Parsippany Plant) 30
Figure 4. Blister Peal Strength Tester (Pfizer Parsippany Plant) 31
Figure 5. Peal Strength Graph 32
Figure 6. The Davinor Layer Gauge 33
Figure 7. Material Distribution Graph 36
Figure 8. Price Comparison Graph 37
LIST OF TABLES
Table 1. Packaging Thermoformer Equipment Setting 23
Table 2. 120 Micron MVTR Test Summary 24
Table 3. 190 Micron MVTR Test Summary 25
Table 4. 240 Micron MVTR Test Summary 26
Table 5. 300Micron MVTR Test Summary 27
Table 6. PVC/PVDC MVTR Test Summary 28
Table 7. MVTR Data Summary 29
Table 8. Vacuum Leak Summary 31
Table 9. Peal Strength Summary 32
Table 10. Optical Layer Gage Summary 34
Table 11. Price Comparison 37
IX
BACKGROUND
Although Regnault prepared some vinyl and/or vinylidene monomers in 1838, and
observed the conversion of the latter to a white powder when exposed to sunlight in sealed tubes,
it is Baumann's polymerization of vinyl chloride (as well as bromide) in 1872 that is often
regarded as the earliest documented preparation of PVC homopolymer (Titow, 1984). But in the
USA, Bakelite was the first truly synthetic polymer discovered and was safer and tougher than
any previously discovered chemically modified variants of natural polymers. Bakelite
(Thermoset) was made from phenol and formaldehyde and had suitable properties to make it an
ideal plastic for electrical appliances. However this plastic had room for improvement, which led
to the discovery and production ofmany more synthetic plastics in the years between the two
WorldWars. Hermann Staudinger, a German chemist, won the 1953 Nobel Prize for Chemistry
for demonstrating that polymers were built from smaller units that had joined together to form
long chains of molecules (Encyclopedia Britannica, 2004). His work laid the foundation for the
great expansion of the thermoplastic industry later in the 20th century.
By the end of the 1930s, commercial production of synthetic polymers was on the rise.
For example, nylon was discovered in the mid 1930's by the chemistWallace Carothers who
worked for the Dupont research laboratory (About, 2004). Nylon was used to make clothing
material and was considered a luxurious novelty. Another discovery was polyvinylchloride
(PVC), which was first produced commercially in the USA in 1933, had an important use as
cable insulation during World War II, and soon after was used for many more applications
(Seymour, 1982).
Polyvinylchloride (PVC) [-(-CH2 -CHCl-)n-] is one of the three most widely used
polymers in the world. This is because PVC is one of the cheapest polymers to make and has a
1
large range of properties that can be used to make hundreds of products. PVC is formed by the
polymerization of vinyl chloride (chloroethane) monomer units. It consists of polar molecules
that are attracted to each other by dipole-dipole interactions due to the electrostatic attractions of
a chlorine atom in one molecule to a hydrogen atom in another atom. These considerable
intermolecular attractions between polymer chains make PVC a fairly strong material.
Uncompounded PVC is colorless and rigid and possesses poor stability towards heat and light.
However, the use of additives and/or stabilizers enables changes the properties of the PVC so it
can be used for countless different applications (Titow, 1984).
During the 1930's, large amounts of chlorine became available in Nazi Germany as a
consequence of a program meant to make Germany independent of imported cotton in case of
war. This program concentrated on the production of rayon, and to this end large amounts of
caustic soda from the chlor-alkali industry were needed. After years of experimenting with
stabilizers, lubricants, and softeners, it was found that fibers could be made from PVC; these had
the added bonus of using up the excess chlorine produced by the expanded chlor-alkali industry.
What had previously been a toxic waste by-product of caustic soda manufacturing, became a
marketable commodity (Greenpeace Austria, 1991).
But the 1970's brought two unforeseen events, both with a major impact and lasting
effects: (1) the oil crisis of 1973/1974, which contributed to the rise of oil prices, and (2) the
discovery that vinyl chloride monomer (VCM) is a carcinogen (Titow, 1984). The oil crisis
caused a serious temporary shortage of oil derivatives, which are an important feedstock for the
production of VCM. This drove the industry to turn to the by-product (waste) of caustic soda to
get the chlorine and hydrogen needed for the HC1.
PVC (POLYVINYL CHLORIDE, VINYL)
PVC is one of the most versatile of the plastic materials; it is also the most dangerous.
PVC is used in packaging such as mineral water bottles, tubs, boxes, cling film, food, and
pharmaceutical packaging. PVC plastic causes greater environmental concern than any other
plastic because the manufacture of PVC is linked to the production of chlorine to an
astronomical degree. Chlorine is a waste byproduct that originates from caustic soda production,
and it is a highly reactive chemical that must be combined with other materials (stabilizers).
Although chlorine compounds are found in nature (the obvious example is sodium chloride, or
common table salt), chlorine manufactured by the chlor-alkali process is quite different. This
chlorine gas is highly reactive; it must therefore be combined with organic compounds (material
containing carbon), and creates organochlorines.
In just a few decades, the chemical industry has distributed millions of tons of
organochlorines per year into our environment. The whole process represents an environmental
disaster. Some of the organochlorines associated with environmental and human health scandals
are familiar names:
Polychlorinated Biphenyls (PCBs), found to stop the reproductive ability of wildlife,
were banned in the late 1970's, although most of the millions of tons produced are
still circulating in the environment (Environment Safety and Health Manual, 2004).
Halons, Chlorofluorocarbon (CFCs), and Carbon Tetrachloride (CC14) will continue
to destroy the ozone layer into the next century even with an immediate ban on their
production (Ozone Depletion Glossary, 2004).
Pesticides - such as Dichloro-diphenyl-trichloroethane (DDT) and Lindane
(Hexachlorocyclohexne-HCH) or commonly known as benzene hexachloride-
are
still being produced.
Organochlorines are found in materials such as PVC as a form of dioxin, which is
known to promote cancer, reduce the efficacy of the immune system, and contribute
to miscarriages and birth deformity. It has been associated with the chemical
industry's worst chemical disasters in Seveso (an air leak disaster in Italy) and Love
Canal (waste dumping in Niagara Falls, NY). Because it literally changes the
functioning of human cells, the effects can be very obvious or very subtle. Because it
changes gene functions, it can cause so-called genetic diseases to appear, and can
interfere with child development. There is no"threshold"
dose - the tiniest amount
can cause damage, and the human body has no defense against it.
PVC creates environmental problems throughout its life cycle. The production of PVC
powder involves the transport of dangerous explosive materials and the creation of toxic wastes.
Then, because PVC on its own is almost useless as a plastic, it must be combined with a number
of chemical additives to make it soft and pliable, heavy metals to make it hard or give it color,
and fungicides to stop bacteria from eating it. Thus, PVC production also gives rise to a huge
secondary and toxic manufacturing industry. The product itself, when bought by the consumer,
can be immediately dangerous. For instance, certain additives, such as those used in flooring,
will evaporate into the air. The most common plasticizer additive is a suspected carcinogen. The
disposal of PVC creates further environmental problems. When burned, it releases an acidic gas,
as well as toxic dioxins and other organochlorines because of its chlorine content; when land
filled; it leaches into the ground and threatens the groundwater supplies. PVC is not a natural
material and will therefore not biodegrade, a feature that the PVC industry is in fact proud of
(Clayton, 1991).
The PVC industry is trying to set up recycling plans, but the range of PVC products
makes it impossible to recycle, since each PVC product contains many different additives. The
industry admits that recycling is expensive and of value primarily from the point of view of
public relations. Meanwhile, our world is filling up with PVC products and the industry is
expanding into Latin America and Asia. PVChas always been a low-price product; after all, it
originated as a method of disposing of industrial waste, and this price advantage is the key to its
success.
PVC Toxicity
PVC is considered by its proponents, such as Norsk Hydro, as an extremely resource
efficient plastic with low energy consumption; nearly 60% of its composition is based on
common table salt, a product available in almost unlimited quantities. What this statement does
not reveal is that in the course of PVC production, common table salt is turned into chlorine gas
and organochlorines, one of the most dangerous group of chemicals ever synthesized. It is this
use of chlorine that distinguishes PVC from other plastics and makes it so dangerous.
The discovery in the 1970's that exposure to VCM could cause certain types of cancer
and other irreversible health hazards affected PVC production for many years. Chlorine and
ethylene are combined to make ethylene dichloride (EDC); the EDC is then used to make VCM.
EDC is highly toxic and easily absorbed through the skin. It causes cancer andbirth defects;
damages the liver, kidneys, and other organs; and can cause internal hemorrhaging and blood
clots. It is also highly flammable: the vapor can explode, generatinghydrogen chloride and
phosgene, two highly toxic gases that can cause Bhopal-typeaccidents. It is impossible to
produce organochlorines without wastes or residues andin the case of PVC production many of
these residues, or tars, used to be incinerated at sea.
The main hazard areas may be collectivelyidentified as the risk of harmful effects on
contact with the PVC materials themselves, or their individual constituents, or decomposition
products, during any of the phases of thematerials'
life history. The principal possible harmful
effects are poisoning, carcinogenic action,irritation or tissue damage, and dermatitis. The form
of contact through which they can arise are ingestion, inhalation,absorption or simply
prolonged/repeated external contact (Titow, 1984). In the US, a legal action for $285 million
dollars was brought by some supermarkets against Borden Chemical Corporation and Goodyear
Tire and Rubber Co. (two PVC polymers producers) based on damage to health attributed PVC
film used to wrap meat (Titow, 1984).
Thermal decomposition of PVC is permitted to occur in a controlled processing area, but
when in accidental fire or as a means of disposal (incinerations), toxic fumes are produced.
These fumes contain considerable proportions of hydrogen chloride (hydrochloric) and hydrogen
fluoride (hydrofluoric) acids. These appear as white fumes, which are highly irritant.
Following the global ban on ocean dumping and ocean incineration agreed to in the early
1990's by the Basel and Bamako convention, PVC residues and wastes are either incinerated
(generating the same type of toxic emissions), sent to landfills, or injected into deep wells.
However, not all waste residues are incinerated, vented, or dumped. Through a process called
chlorolysis, approximately a third of these residues are turned into new chlorinated products.
Many are familiar: the chlorinated solvent perchlorethylene is the common dry cleaning fluid
and a suspected carcinogen; carbon tetrachloride is an ozone-depleting chemical and a known
human carcinogen. Other uses of chemical by products include pesticides, CFCs, cleaning fluids,
and the fragrance used in toilet products and for coffins.
As is true of all chlorine-containing products, these new applications spread more toxic
emissions into the air, soil, and water. Through the use of unnecessary toilet disinfections,
organochlorines have for years been washed into the sewer system. The use of similar products
in coffins causes highly toxic emissions such as dioxins from crematoria.
The VCM made from EDC is an extremely toxic, flammable, explosive and carcinogenic
gas. Symptoms of VCM poisoning include softening of bones, deformation of fingers, skin
complaints, impotence, bad circulation and shortness of breath, liver damage and even a special
form of liver cancer, angiosarcoma. Strict standards have consequently been set in many
countries to limit worker exposure, as well as the amount of un-polymerized VCM allowed to
remain in finished products, although these standards may not exist in foreign factories or their
products. However, standards can never solve the problem. VCM is impossible to contain within
a plant no matter how tight the system. The reality is that the chemicals used to produce PVCare
toxic; it is impossible to contain all these chemicals during manufacture no matter how
sophisticated and well monitored the plant is; and the risk of spills, accidents, and bad on-site
management only intensifies the problem.
The first limits recommended in the United Kingdom (in the mid-1970s) for a maximum
VCM concentration in factory atmosphere started with a time weighted average figure of 25 ppm
(by volume), soon to be reduced to 10 ppm with further provision that whenever possible zero
concentration should be aimed at (UK Health and Safety Executive, 1975). In the meantime, the
US Food and Drug Administration limited VCM concentrations to lppm and prohibited the use
of rigid and semi-rigid PVC for food packaging applications (bottles, film etc.) unless it could
shown that no migration of VCM into the content would occur. Through extensive research and
testing, the levels of VCM were reduced to undetectable levels in the unplasticised PVC. But the
fact remains that only complete avoidance of exposure toVCM can entirely eliminate the risk.
Transport Nightmare
In view of the nature of VCM, it is extremely disturbing that most of the vast quantity of
VCM produced worldwide is manufactured far from where it will be eventually polymerized into
PVC. It is therefore transported around the world from industrial plant to industrial plant, by
road, rail, and sea.
The risk of accidents represents dangers to communities living along these transport
routes. When transported, VCM is compressed and liquefied. Any leaks can lead to explosions,
since ignition temperatures and critical temperatures are both low (minus 77 and below 160
degrees Celsius, respectively). When VCM escapes, it forms pools of mist which, being heavier
than air, creep along the ground. If ignited, they will flash back to the source of leakage. Large
VCM fires are almost impossible to contain. VCM is only slightly soluble in water and reverts to
a gaseous state quickly, floating above the water until it forms a gas. On the water surface, it
combines with air to form explosive mixtures. VCM leaked into sewage systems is also highly
explosive. Serious rail transport accidents involving VCM are well documented; at least 17 took
place between 1964 and 1980.
Packaging ShelfLife
Packaging shelf life is divided between long shelf life and short shelf life. Products that
are packaged with a short shelf life-
typically two years or less before they are thrown away-
are usually small in size. Examples of products with short shelf life include pharmaceutical
products, medical supplies, and office supplies. PVC is a major packaging material for these
short shelf life packages. All the problems associated with PVC also apply to PVDC and CTFE,
another chlorinated plastic widely used in packaging. An inherent characteristic of packaging
with a short lifespan is that once it has served the purposes of display, containment, and
protection, it becomes waste- light but voluminous.
Is PVCRecyclable?
A major goal set by the PVC industry to improve its image is to create the impression
that PVC is an environmentally acceptable material, one that can be recycled. The US plastics
industry has noted that the image of plastics among consumers is deteriorating at an alarmingly
fast pace. In response to this increased public awareness, the plastics industry launched two
major public relations efforts. The first was to demonstrate the biodegradability of plastics,
which failed miserably. Their second effort has been more successful. Their strategy has been to
8
build on society's positive response to recycling while increasing PVC's market share and
avoiding any attempt to legislate product bans or restrictions. In reality, post-consumer plastics
recycling is negligible, despite the fact that the PVC industry feels itself under intense pressure to
prove the recyclability of chlorine containing plastic. That pressure has been increased by the
fact that Denmark, Sweden, Switzerland, Germany, and Austria have placed restrictions on PVC
packaging owing to the incineration problems it presents.
PVC belongs to the family of plastics known as thermoplastics. These plastics, which
include polyethylene, polypropylene and polystyrene, can be remelted and reformed, in contrast
with the thermosets such as polyurethane, which cannot be re-melted or reformed. PVC can
therefore theoretically be recycled, and reprocessing of scrap during production routinely takes
place, usually in the interests of production economics rather than of environmental protection.
Genuine recycling, however, is post consumer, which takes place with products that have already
completed a useful life. Attempts to recycle these post consumer PVC plastics are fraught with
problems.
PVCDisposal
Dealing with PVC waste involves special considerations such as selective reclamation
(e.g., separation from waste mixture with other plastics), which is not a simple task because of
the many additives that are contained in the variant of PVC material. Reprocessing is just as
complicated because of the side variety of the PVC formulations and the increased susceptibility
to heat degradation in re-processing (Titow, 1984).
One statement can be made with absolute certainty: PVC products will end up as waste.
This is not only because of the nature of the productsmade from PVC products, many of which
are cheap, mass produced consumer goods that have a short life and cannot be repaired, but also
because of the many formulations and additivespresent in different PVC products make them
impossible to recycle in the true sense of the word. Even the few products that are made from
post consumer PVC discarded products will sooner or later end up in the trash-
usually sooner.
Currently, millions of tons of PVC products are disposed of by incineration or landfill,
the costs of which are borne by the general public both in economic and human health terms.
Tests have shown that toxic stabilizers (barium/cadmium) can be leached from plasticized PVC
under landfill conditions. Plants can absorb these heavy metals, and products containing them
should not be disposed of in normal landfills. Even in a well-managed landfill, the composition
of the leachate (the liquid seeping through the body of the landfill) is unpredictable, varying with
the nature of the land filled waste, the amount of rainfall, the temperature, and a host of other
factors. The increasing volume of PVC being land filled, and the fact that not even the best
landfill membranes can prevent leachate escaping into the outside environment, set the scene for
future pollution of aquifers supplying drinking water.
Many countries incinerate a large proportion of their municipal solid waste, sometimes
with energy recovery. The chemical industry supports this method of waste management and has
coined the term "whitecoal"
to validate the use of waste plastics as a fuel. But the chlorine
content of PVC makes it completely unsuitable for incineration. Whenever chlorine is burned,
HCI (hydrogen chloride) is formed. This poisonous, corrosive substance must be removed from
flue gases to avoid serious environmental pollution, and this entails high capital investment,
efficient monitoring, and sizeable amounts of energy. Also, incinerators are easily damaged by
the corrosion that is generated by hydrogen chloride. It was for this reason in fact that the
chlorine and PVC industry created ocean incineration since the emissions were not captured by
scrubbers but spewed onto the ocean surface.
10
PVC is also one of the greatest sources of dioxins and other organochlorines. The
incineration of a kilogram of PVC produces up to 50 micrograms of dioxin (TEQ), enough to
initiate cancer in 50,000 laboratory animals. Recent evidence of dioxin's toxicity details
reproductive problems in offspring of parents contaminated with low levels of dioxins. Hormone
changes and both demasculinization and defeminization of both sexes are now occurring in
wildlife populations. Incineration also produces toxic ash that must be disposed of in landfills. In
the case of PVC, for every 1 ton of PVC burned, 0.9 tons of waste salts are created. Because
these are contaminated with heavy metals or whatever additives there were in the PVC products
the salt must be disposed of. The costs of such emission cleaning and disposal are actually higher
than the cost of the new PVC product.
Finally, the PVC industry, well aware of the negative public image of their product, has
evolved an intriguing public relations concept: the "closed chlorinecycle."
Briefly, the acidic gas
from the incinerator is neutralized using large quantities of caustic soda to produce salt. This, the
industry maintains, is then re-introduced into the process to produce more chlorine and hence
PVC. In reality this only perpetuates MORE production of chlorine, rather than closing the cycle
because the production of caustic soda entails the production of almost equal amounts of
chlorine. Also the salts that are created after neutralization are usually contaminated with heavy
metals and other additives contained in the various PVC products thereby preventing their re-use.
It is obvious that the only solution for closing the PVC cycle is not to produce the product in the
first place.
PVC Illusion
The PVC industry advocates that its product is vital to modern society, and points to the
fact that PVC is used widely almost everywhere.This development is not due to the superior
qualities of PVC, but rather to the fact that it can price undercut many traditional materials such
11
as wood, metals, or glass. However, if costs as a whole are considered, rather than merely the
purchase price of a PVC product, traditional materials will be seen to be more economical in the
long-term. Forward-looking companies, local authorities, and institutions have been becoming
increasingly aware of the threats posed by PVC and many have taken action.
The dangers posed by PVC products are now understood. The PVC industry, recognizing
that market saturation has been achieved in Western Europe and North America, is now planning
to expand to the newly- and less- industrialized countries. It is now paramount that this toxic
industry must not expand and that PVC bans and phase-outs must become an urgent priority for
both hemispheres.
Victims ofthe PVC Industry
Here are two vivid examples of victims of the PVC industry.
Fresh out of the Air Force, Dan Ross went to work for a Conoco vinyl chloride-producing
plant in Lake Charles, Louisiana in 1967. Dan's widow, Elaine, fell in love at first sight, and
after being married to him for 25 years, she says he could walk into a room and still take her
breath away. But his job was taking his breath away.
Elaine recalls, he came home from work one day, and he was taking off his boots and
socks, and I looked at his feet. The whole top of them were burned where the chemicals
had gone through his boots. I said, "My God, what was it that goes through leather,steel-
toed boots and your socks to dothat?"
As the years went by you could see it on his face. He started to get this hollow look under
his eyes, and I could always smell the chemicals on him. I could even smell it on his
breath after a while. But even up until he was diagnosed the first time, he said, "They'll
take care of me. They're my friends."(PBS.org, 2004)
In 1989, Dan Ross was diagnosed with a rare form of brain cancer, and 10 years after
Dan's death and a million pages of industry documents uncovered that exposure to PVC was the
ultimate cause.
12
Bernard Skaggs landed a job with the BF Goodrich plant in Louisville, Kentucky, in
1955. The factory mixed vinyl chloride gas into a gooey dough that was then dried and processed
into pellets for PVC plastic. When Bernie Skaggs started having problems with his hands, he
first went to the company doctor-
who assured him the condition was not related to his work.
"My hands began to get sore, and they began to swell some. My fingers got so sore on the
ends, I couldn't button a shirt, couldn't dial a phone. And I had thick skin like it was
burned all over the back ofmy hand, back ofmy fingers, all the way up under my arm,almost to my arm pit. And after enough time, I got like thick places on my face, right
under myeyes."
(PBS.org, 2004)
Bernie's hands were eventually x-rayed. He was shocked looking at x-rays that showed
the bones in his fingertips had disappeared; his bones were being destroyed. The condition is
called acroosteolysis.
Thousands of other lives have been destroyed due to the silent killer (PVC). No one today
can avoid synthetic chemicals, but there are steps that people can take. The way to reduce the
dioxin threat is to stop burning trash and to stop producing PVC and other chlorinated chemicals.
If your town sends its trash to an incinerator, tell your town officials to institute comprehensive
recycling. Write to companies that use vinyl and ask them to use the known safe substitutes. Ask
your supermarket and office supply stores to sell Totally Chlorine Free (TCF) products. Learn
more about the dioxin threat. Read the books Dying From Dioxin by Lois Gibbs, and Our Stolen
Future by Theo Colborn. Talk to your friends and neighbors about dioxin and what you can do to
reduce the threat. "The Right-to-Know"
laws have made it possible for citizens to identify
specific companies and/or products that release the most toxic chemicals identified by the EPA.
13
AN ALTERNATIVE TO PVC FOR PHARMACEUTICAL PACKAGING
An alternate material to polyvinylchloride (PVC) based materials that is not harmful to
the environment and not corrosive to the equipment is currently available for use in the
pharmaceutical industry. Cyclic Olefin Copolymers (COC) has the properties to protect the
product while it is environmentally safer than PVC.
As pharmaceutical manufacturers adopt blister packaging at a breathtaking rate, newer,
environmentally friendly, more efficient plastic materials are available to keep up with
performance demand. A pharmaceutical packaging market study revealed that currently
traditional plastic bottles (i.e., High Density Polyethylene (HDPE)) with closures retain a
considerable market share 30% - 35%, and the unit dose packages (blisters) make up 20% 25%
(CMS Info., 2004). The blister packaging market share will expand based on the anticipated
adoption of new FDA regulations requiring unit dose containers for institutional drugs, and will
generate above average growth opportunities and remain the leading type of pharmaceutical
packaging in value terms (Mindbranch.com, 2004).
Most new drugs are extremely hydroscopic; therefore, the pharmaceutical industry has
high standards for material performance. Water vapor transmission rate (WVTR), odor
permeation, impact protection, clarity, and formability are some of the characteristics that a
product must be tested against before the material is approved for pharmaceutical packaging. The
pharmaceutical industry has favored monolayer polyvinyl chloride (PVC), two layer coated
polyvinylidene chloride (PVDC), polypropylene (PP,) and chlorotrifluoroethylene (CTFE) with
base material Aclar. Most of the widely used plastics in the pharmaceutical industry give off
hydrochloric and hydrofluoric acids when heated and incinerated. Regulations in Europe and
Asia are discouraging the use of these materials for packaging purposes. Environmentally
14
friendly olefin plastics like Cyclic Olefin Copolymers provide long-term protection from
moisture comparable to that of PVDC and CTFE. And with its low density, it yields more film
per pound of resin.
COC (OLEFIN POLYMER)
The original patent of Eleuterio in 1957 reported the ring-opening polymerization of
cyclopentene, norbornene, etc. was the grounding breaking for a new family of Olefins (H. S.
Eleuterio, 1957). Cyclic Olefin copolymers, COC, are an interesting group ofmaterials that have
received increasing attention of late. These newly commercialized materials bring to the
marketplace a unique combination of properties that can be utilized in package development.
Development and Structure ofCOC
Cyclic Olefin copolymers are not new compositions ofmatter, having been known for
almost half a century. Particularly relevant are the efforts at the Leuna, near Leipzig in the
former East Germany, to copolymerize ethylene and norbornene over 30 years ago. Later, Mitsui
Petrochemical in Japan started to work on copolymers of ethylene and another cyclic olefin.
Both this work and that at Leuna were based on Ziegler/Natta type catalysts (Imamolgu, 1990).
Polymers based on this catalyst technology are more limited in product range, economics, and
purity than those based on metallocene catalysis. In the 1980's concentrated development of
COCs prepared via metallocene catalysis was undertaken (Draguta, 1985).
Manufacturing ofCOC
COC consists of an olefin copolymerized with a cyclic olefin. There are several COCs
available, produced by conventional addition polymerization. They are based on different cyclic
olefins. In the case of Topas COC, norbornene is the Cyclic Olefin used. Norbornene is produced
15
by the Diels-Alder addition of ethylene to cyclopentadiene. This is then reacted with ethylene in
the presence of a metallocene catalyst to form COC.
COCs are actually a family of polymers differentiated mainly by the heat resistance of the
materials. These polymers are all completely amorphous, statistically random copolymers with
no measurable degree of crystallinity. This is the result of the chain stiffening effect and bulky
nature of the norbornene comonomer. The other major variable, molecular weight, determines
the rheological properties.
The family of COC resins is fully amorphous and shares many common features. The
exceptional purity and absence of chromophores in COC resins makes them both glass clear and
water white. Mechanically, these materials are strong, stiff and brittle, very much like PVC or
PS.
COC in Flexible Films
COCs can be used in two ways in packaging films: as an individual layer of COC (mono
COC) or multilayer structure. With a multilayer, the moisture barrier will be the highest. The
COC layer will contribute significantly to film stiffness. In the case of very thick COC layers, the
films can be thermoformed for pharmaceutical blister packs. A second, and possibly more widely
applicable way to use COCs in packaging would be as a blend in polyolefins to accomplish
specific modification of the film. COCs alter the characteristics of polyolefin films in many
ways. They increase the modulus, maintain or lower the haze, reduce the COF and blocking
tendency, improve sealing behavior and improve the MVTR for the polyolefin. Any one of these
improvements may not be enough to justify its use; but taken in total, these benefits allow for
innovative design of film structures. The increased modulus of the blends can allow for down
gauging of the film at equivalent stiffness; or create a stiffer film at the original film gauge; or an
intermediate combination, which will satisfy the design and economic constraints.
16
COC also improves the hot tack strength. The absolute value of the hot tack force is
increased significantly, and the peak force is extended over a wider temperature range than the
base resin. This can translate to faster packaging line speeds and less delamination since the
package seals are stronger at higher temperatures. As mentioned earlier. While polyolefins are
not considered to be good moisture barriers, COCs have excellent moisture barrier. COCs can
improve theMVTR of these materials. This can influence the shelf life of moisture sensitive
products.
There are many factors to be considered in the design of flexible packaging films. Among
these are the appearance of the film, what is to be packaged, film properties desired, package
economics, and esthetics. In the case ofmultiplayer films, the properties are a blend of the
properties of the individual layers and how they are arranged.
Environmentally Safe Blister Packaging with ImprovedBarrier Properties
The packaging of medicines has to meet particularly demanding criteria. These include
bio-compatibility, reliable protection against external influences, optimum shelf life, clear
identification, and easy of handling and dispensing. For medicines in tablet form, blister packs
have become the standard. They not only meet all technical conditions required by
pharmaceutical companies, but they are also easy and safe for use by patients. A safe,easy-to-
use package promotes the patient's compliance to directed dosage, a crucial factor for successful
treatment. Each individual tablet is clearly visible and can easily be pushed through the
aluminum foil. A key component is the plastic film, which, in combination with the aluminum
foil that forms the base, covers the tablets at the top in a blister pack. The plastic film must have
the highest possible transparency and simultaneously provide protection against moisture and
(for sensitive products) oxygen. The combination of high moisture barrier, clarity, and
thermoformability supports use of COC in pharmaceutical blister and personal care packaging.
17
When blended with polyolefins, COC dramatically increases stiffness allowing down gauging of
films (Capus, 2001).
Processing
COC can be compounded with pigments, lubricants, glass fibers, flame-retardants and
other additives and fillers. It can be processed by a range ofmethods, including injection
molding; film, sheet and profile extrusion; and injection blow molding. Drying and other special
pretreatments are not needed. Extruded COC films can be biaxially stretched for use in
capacitors, monoaxially stretched for shrink-wrap applications, or used as is in laminates. Biaxial
orientation greatly improves film mechanical properties. COC can be coextruded with low
density PE without a tie layer, but with other resins, such as PP, polyester, nylon, ethylene vinyl
alcohol or PC, a tie layer is generally required for good adhesion.
Properties ofCOC (Provided by Ticona a division of Celanese, Summit, New Jersey )
Density 1.02 g/cc
Water absorption <0.01 %
Water vapor permeability @ 85%RH 0.02-0.04 g/m2/ day
Tensile strength 9,570 psi
Elongation @ break 3-10 %
Tensile modulus 377-464 kpsi
Flexural modulus 0.5 Mpsi
Modulus of elasticity, Tg > 100C 3,100-3,300 Mpa
Charpy impact 13-20kJ/m2
Notched charpy impact 1.7-2.6kJ/m2
Hardness 89 Shore D
Glass transition temperature 70-180 C
Heat deflection temperature @ 66 psi 75-170 C
Melt Flow Index at 260C 12-55 g/10 min.
Dielectric constant @ 60 Hz 2.35
18
Dielectric loss @ 60 Hz <0.02 %
Dielectric breakdown 30 KV/mm
Comparative tracking index >600 volts
Volume resistivity >10 16 ohm-cm
Light transmission 92 %
Refractive index 1.533
Pharmaceutical Blister Packaging Requirements
Pharmaceutical packaging constitutes an interesting growth market for COC because it
has to meet a diversity of requirements. It must protect the contents; it must be easy to handle
and open; it must be tamper-proof; and it must provide the patient with all necessary information.
Blister packs have proved ideal for pharmaceutical products in tablet form. The combination of a
transparent plastic film with an aluminum foil renders each individual tablet visible. The user can
remove the tablet simply by pressing it through the foil. The other tablets remain well protected
until it is their turn to be taken. Moreover, its manufacture is less costly than the process of
sealing tablets between two layers of aluminum foil. Extreme demands are made on the plastic
film or, to be more precise, on its barrier effect against moisture vapor transmission rate
(MVTR) when the blister pack is to be used in tropical regions, that is to say, in regions where
high temperatures and a high relative humidity prevail. In such cases, the blister pack must meet
the following requirements:
It must reliably protect the tablets, which often contain hydroscopic sensitive
compounds, against moisture for a period of at least two years.
It must be tamper proof, both in respect to the packaging as a whole and the
packaging of each individual tablet, thus guaranteeingthe genuineness of the
contents.
It must be possible to sell the tablets individually.
It must afford a high degree of protection against counterfeiting (product piracy).
19
In order to improve the functional properties of blister packs, the COC film is coated on
both sides with a thin layer of polypropylene. These layers not only improve the tensile impact
strength of the relatively brittle COC film, but also add high grease resistance to its existing
water vapor impermeability. Moreover, the packaging industry has already had many years of
practical experience with polypropylene as a packaging material with direct contact with
pharmaceuticals products, making any further large scale, time-consuming trials unnecessary.
The water vapor impermeability increases in direct relation to the increase in the thickness of the
COC layer.
TEST RESULTS
Research was conducted to compare olefin structures (such as PP/COC/PP) to halogen
based material (e.g., PVC/PVDC) that corrode equipment and/or form toxic hydrofluoric and
hydrochloric acids. The following standard COC film structures were used in the testing:
COC Coex Film 120 micron - 20 micron PP / 45 micron PE tie layer / 120 micron
COC / 45 micron PE tie layer / 20 micron PP (total thickness 250 micron).
COC Coex Film 190 micron - 20 micron PP / 20 micron PE tie layer / 190 micron
COC / 20 micron PE tie layer / 20 micron PP (total thickness 270 micron).
COC Coex Film 240 micron - 20 micron PP / 20 micron PE tie layer / 240 micron
COC / 20 micron PE tie layer / 20 micron PP (total thickness 320 micron).
COC Coex Film 300 micron - 20 micron PP / 20 micron PE tie layer / 300 micron
COC / 20 micron PE tie layer / 20 micron PP (total thickness 380 micron).
These COC structures were tested against
These COC films were compared to a control package of PVC coated PVDC with the following
properties: Klockner PVC/PVDC Barrier film 200/25/40 (200 micron PVC, 25 micron PE,
coated with 40 g/m2 PVDC (total thickness 200 micron). The COC and PVC films were
compared based on the following criteria:
20
MVTR - to determine the moisture permeation of a unit dose blister using test
method - United States Pharmacopeia USP25 <671> titled "Single-Unit Containers
and Unit-Dose Containers For Capsules and Tablets"(United States Pharmacopeia
Convention, Inc., 2001).
Vacuum Leak Test
Peel strength test
Layer distribution
Machine-ability and form-ability
Price comparison based on surface area
The results of the study, and a discussion of how COCs can be utilized effectively in the
design of flexible films, is described below.
MVTR
On an Uhlmann thermoformer (Model # UPS4 MT - see Figure 1) line at the Pfizer plant
in Parsippany, NJ, approximately 10,000 blisters of each of the following structures were
formed.
COC Coex Film 120 micron - 20 micron PP / 45 micron PE tie layer / 120 micron
COC / 45 micron PE tie layer / 20 micron PP (total thickness 250 micron).
COC Coex Film 190 micron - 20 micron PP / 20 micron PE tie layer / 190 micron
COC / 20 micron PE tie layer / 20 micron PP (total thickness 270 micron).
COC Coex Film 240 micron - 20 micron PP / 20 micron PE tie layer / 240 micron
COC / 20 micron PE tie layer / 20 micron PP (total thickness 320 micron).
COC Coex Film 300 micron - 20 micron PP / 20 micron PE tie layer / 300 micron
COC / 20 micron PE tie layer / 20 micron PP (total thickness 380 micron).
Klockner PVC/PVDC Barrier film 200/25/40 (25 micron PVC coated with 40 g/m2
PVDC (total thickness 200 micron).
21
Figure 1. Uhlmann Thermoformer, Model # UPS4 MT (Pfizer Parsippany Plant).
22
The tooling that was used to form all of the test sets is the same tooling that is used for
the production of Zyrtec (single dose). The tooling is a 9 up design (3x3 configuration). To
minimize variability in the test method I held certain equipment settings as constant as I was able
i.e. the speed and sealing temperature were not varied as long as I had was able to achieve a good
sealed blisters. The criteria for a good blister is that it would pass the leak test, the appearance of
the cavity is well defined and the foil backing is within the specification. The upper and lower
preheat temperatures were modified slightly to achieve a fully formed cavity. The machine
settings are summarized in Table 1.
Table 1. Packaging Thermoformer Equipment Setting.
Equipment Settings COC 120 COC 190 COC 240 COC 300 PVC/PVDC
Forming Preheat Upper
Temperature (degrees Celsius)
110/115/120 110/115/120 110/115/125 110/115/125 110/115/120
Forming Preheat Lower
Temperature (degrees Celsius)
110/115/120 110/115/120 110/115/125 110/115/125 110/115/120
Sealing Temperature (degrees
Celsius)
185 185 185 185 185
Machine Speed (cycles per
minute/blisters per minute)
40/360 40/360 40/360 40/360 40 / 360
Nine (9) samples representing one stroke (cycle) from each film configuration were filled
with 75 mg desiccant and marked appropriately. Samples were placed in an Environmental
Chamber (Model* Canon 6030 Unit #4 SN# 042503-6656-04) set at 23 degrees C with 75%
humidity. The environmental chamber was calibrated on 03-12-04; the next due date for
calibration is 09-12-04. Samples were weighed at 0 days, 1 day, 2 days, 3 days, 8 days, and 36
days. The weights were measured on an electronic balance (Model # Mettler Toledo AE163
serial number F30461) whose balance was calibrated on 03-04-2004; the next calibration is due
sometime in September 2004. The results were recorded (see Tables 2-7 and Figure 2 on the
following pages) and a report summarizing the results was approved.
23
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Table 7. MVTR Data Summary.
Rate ofMoisture Permeation (mg/day)
COC 120 COC 190 COC 240 COC 300 PVC/PVDC
Time Elapsed Max Min Max Min Max Min Max Min Max Min
24 hours (day 2 - day 1) 0.800 0.200 0.600 0.200 0.200 -0.200 0.100 -0.200 -0.300 -0.800
48 hours (day 3 - day 1) 0.300 0.050 -0.100 -0.200 -0.100 -0.250 -0.050 -0.150 -0.050 -0.200
7 days (day 8 - day 1) 0.043 -0.043 0.114 0.029 0.157 0.100 -0.014 -0.043 -0.014 -0.071
28 days (day 36 - day 8) 0.071 0.046 0.033 0.014 0.004 -0.014 0.061 0.043 0.079 0.061
According to the USP 25 test method <671> all of the samples meet class"A"
specification
since none of the samples exceeded the 0.500 mg/day at the 28 days test.
-0.02
Rate ofMoisture Permeation (mg/day)
Film
? COC 120 Max
COC 120 Min
? COC 190 Max
? COC 190 Min
COC 240 Max
B COC 240 Min
COC 300 Max
? COC 300 Min
PVC/PVDC Max
PVC/PVDC Min
Figure 2. MVTR Data Graph.
Note-COC 240 minimum daily permeation ended up
in the negative region (-0.014 mg/day) is
due to the measurement of a very narrowrange with an analytical scale of 0.010 milligram
statistical noise.
29
Vacuum Leak Test
A Vacuum Leak Test was completed on 9 blisters randomly picked from the 10,000
blisters for each film configuration. The Vacuum Leak Tester that was used (Model # ATS Item
# 1 109 -
see Figure 3) was last calibrated on 4-30-2004; the next calibration is due July 2004. A
digital stopwatch was also used; it was last calibrated on 4-13-2004 with its next calibration due
April 2005.
Figure 3. Blister Vacuum Leak Tester (Pfizer Parsippany Plant).
The vacuum chamber was filled with water and a red dye solution which contained FD+C
red 40 CAS 25956-17-6. The product was placed inside the chamber and a weight was placed on
the samples to keep them submersed. The weight contained holes to keep the vacuum pressure.
The vacuum pump was turned on until thevacuum pressure reached 15 PSI. After a 60 second
wait, the vacuum pump was turned off andthen opened once it reached equilibrium pressure.
The product was then removed from the vacuum chamber and rinsed in clear water, and the
30
samples tapped dry. The sample cavities were then checked for the red liquid. The results are
recorded in Table 8 below.
Table 8. Vacuum Leak Summary.
Vacuum Leak Test
COC 120 COC 190 COC 240 COC 300 PVC/PVDC
Blister #1 Pass Pass Pass Pass Pass
Blister #2 Pass Pass Pass Pass Pass
Blister #3 Pass Pass Pass Pass Pass
Blister #4 Pass Pass Pass Pass Pass
Blister #5 Pass Pass Pass Pass Pass
Blister #6 Pass Pass Pass Pass Pass
Blister #7 Pass Pass Pass Pass Pass
Blister #8 Pass Pass Pass Pass Pass
Blister #9 Pass Pass Pass Pass Pass
Peal Strength Test
A Chatillon Peal Test Machine (Model # LTCM-5 Serial # 13377 - see Figure 4), last
calibrated on 08-14-2003 and due to be recalibrated in August 2004, was used to test the bonding
of the film to the foil.
Figure 4. Blister Peal Strength Tester (Pfizer ParsippanyPlant).
31
IT-1125 was the test protocol used to test the blisters listed in Table 9. Results of the test are
shown in Figure 5.
Table 9. Peal Strength Summary.
Peal Strength Test (lbs.)
COC 120 COC 190 COC 240 COC 300PVC/PVDC
(control)Blister #1 3.41 6.42 5.52 6.43 1.64
Blister #2 4.04 5.13 5.39 5.48 3.56
Blister #3 5.60 6.05 5.34 5.94 1.61
Blister #4 5.18 5.71 4.95 6.36 0.46
Blister #5 11.10 5.54 5.49 6.02 4.82
Blister #6 5.86 5.72 5.87 8.02 1.36
Blister #7 7.71 6.20 5.74 5.83 2.80
Blister #8 7.55 5.81 6.71 7.43 5.24
Blister #9 5.19 5.84 5.90 8.16 6.22
Average 6.18 5.82 5.66 6.63 3.08
?Percent
ofControl201% 189% 184% 215% N/A
* Percent ofcontrol= the COC average peal strength divided by the average control peal
strength (PVC/PVDC)
Peal Strength Test
COC 120
? COC 190
COC 240
COC 300
H PVC/PVDC
COC 120 COC 190 COC 240 COC 300 PVC/PVDC
Figure 5. Peal Strength Graph.
32
Optical Layer Gauge
A Davinor Layer Gauge (Model # IID Multilayer Thickness Gauging, Serial No. #109
rr-1 125) was used to test the distribution of the different layers within the cavity. Davinor Inc.
calibrates the instrument annually.
Detector signal
Figure 6. The Davinor Layer Gauge (Davinor, 2004).
The Davinor Layer Gauge instrument (see Figure 6) is designed to measure thickness of
the individual layers ofmultilayer materials. Its main targets of application are transparent and
semi transparent multilayer plastic films. On the basis of its structure, the Layer Gauge is
suitable for a measuring of especially thin film materials (Davinor, 2004). The testing results are
shown in Table 10 and Figure 7 that follow.
33
Table 10. Optical Layer Gage Summary.
COC 12C) COC 190
Preformed Film Preformed Film
Measurement (micron) PP COC PP Measurement (micron) PP COC PP
1 65.9 126.5 67.2 1 36.4 208 37.7
2 67.9 127.8 67.8 2 36.4 208 36.9
3 67.4 126.5 65.8 3 36.9 208 36.7
Average 67.1 126.9 66.9 Average 36.6 208.0 37.1
Blister 1 Blister 1
Measurement (micron) PP COC PP Measurement (micron) PP COC PP
Side 33.8 63.5 31.9 Side 23 121.7 21
Top 43.9 87.5 43.4 Top 25.9 126 23.9
Blister 2 Blister 2
Measurement (micron) PP COC PP Measurement (micron) PP COC PP
Side 39.6 76.2 40.6 Side 22.7 126.7 26
Top 43.9 84.7 44.7 Top 27.3 136 25.4
Blister 3 Blister 3
Measurement (micron) PP COC PP Measurement (micron) PP COC PP
Side 33.3 83.3 33.1 Side 19.4 98.9 19.5
Top 44.6 85.3 44.9 Top 23.7 132 25.4
Top Average 44.1 85.8 44.3 Top Average 25.6 131.3 24.9
Side Average 35.6 74.3 35.2 Side Average 21.7 115.8 22.16667
COC 24() COC 300
Preformed Film Preformed Film
Measurement (micron) PP COC PP Measurement (micron) PP COC PP
1 35.8 254.9 37.8 1 40 307 43.5
2 34.4 253.5 36.3 2 42.8 305.6 42.1
3 34.4 254.5 36.3 3 41.4 308.4 43.6
Average 34.9 254.3 36.8 Average 41.4 307 43.1
Blister 1 Blister 1
Measurement (micron) PP COC PP Measurement (micron) PP COC PP
Side 20.5 121.4 18.5 Side 18.9 165.6 20.2
Top 25.9 153.8 23.2 Top 21.6 189.8 24.7
Blister 2 Blister 2
Measurement (micron) PP COC PP Measurement (micron) PP COC PP
Side 18.7 113.9 17.4 Side 15.2 190.4 24.6
Top 28.8 160.9 29 Top 17.3 211 29.1
Blister 3 Blister 3
Measurement (micron) PP COC PP Measurement (micron) PP COC PP
Side 24.4 126.5 23.2
29
Side 15.8 184.3 20.2
Top 28.8 159.4 Top 20 200 26.1
Top Average 27.8 158.0 27.1 Top Average 19.6 200.3 26.6
Side Average 21.2 120.6 19.7 Side Average 16.6 180.1 21.66667
(Tab e continues)
34
Table 10 (continued)
PVDC-PE-PVC
Preformed Film
Measurement PVDC PE PVC
1 22.4282 34.3154 205.5368
2 21.7678 34.3154 204.089
3 22.4282 33.9852 203.0476
Average 22.208 34.205 204.224
Measurement
Side
Top
PVDC
9.525
9.525
Blister 1
PE
15.7226
17.8308
PVC
103.9876
15.7226
Blister 2
Measurement PVDC PE PVC
Side 12.192 19.9898 116.459
Top 11.5824 18.5166 116.5606
Blister 3
Measurement PVDC PE PVC
Side 11.0998 18.0086 118.2878
Top 10.8712 20.701 115.189
Top Average 10.660 19.016 82.491
Side Average 10.939 17.907 112.911
Summary ofMaterial Distribution
COC 120 COC 190 COC 240 COC 300 PVC/PVDC
Preformed 260.9 281.7 326 391.5 260.4
Top 174.3 181.9 212.9 246.5 112.2
Side 145.1 159.6 161.5 218.4 141.8
Top as a % ofpreformed 67% 65% 65% 63% 43%
Side as a % of preformed 56% 57% 50% 56% 54%
35
Material Distribution
? Preformed
Top
DSide
COC 120 COC 190 COC 240 COC 300 PVDC/PVC
80%
70%
60%
50%
40%
30%
20%
10%
0%
Material Distribution
? Top as a % of preformed
Side as a % of preformed
COC 120 COC 190 COC 240 COC 300 PVDC/PVC
Figure 7. Material Distribution Graph.
36
Price Comparison
Converters of the COC and PVC/PVDC materials generated the prices. All prices were
based on 20,000 kg annual volume. Results are shown in Table 11 and Figure 8 below.
Table 11. Price Comparison.
$/kg $/lbs $/1000 square inches
COC 120 $9.24 $4.20 $1.41
COC 190 $9.46 $4.30 $1.60
COC 240 $10.12 $4.60 $1.99
COC 300 $10.45 $4.75r
$2.43
PVC/PVDC $4.38 $1.99 $1.31
Price Comparison
G
,0
<P 5>fS>
G
.0
\
0
.0
V
G
,0
<*
A'o
A9,0
Figure 8. Price Comparison Graph.
The COC family yields more area per kg,which makes the material somewhat competitive in
pricing to the PVC/PVDC or Aclar family.
37
CONCLUSION
The following is a summary of the test results:
TheMVTR for the COC family is slightly better than that of PVC/PVDC and both
meet the USP class"A"
designation.
The vacuum leak test passed for all of the material.
The Peel strength test on an average was twice as good for the COC than that of
PVC/PVDC.
The material distribution is also better for the COC family that that of PVC/PVDC.
The machine-ability and form-ability was the same for both; the equipment produced
10,000 blisters at a rate of 40 cycles/minute or 360 blisters/minute. However,
excessive static build up was noticed during the die cutting of the COC. This could
present frequent stoppages if the static is not alleviated. There are a few different
methods currently available that reduce or even eliminate static build up, such as
static bars, ionized air, grounding of the die cutting tool, etc. Also, all of the PVC
based families corrode the tooling, which requires frequent and costly repair or the
purchase of a new tool. COC is an Olefin material, which does not affect the tooling
in any form.
The price of COC is equally competitive to the COC 120 and slightly higher to the
COC 190, but 52% and 85% higher than COC 240 and COC 300, respectively.
However, once COC is accepted by the pharmaceutical industry and production
volume increase, it is predicted that the price will come down to competewith other
materials. Based on the potential health hazard of PVC and its family ofmaterials, the
cost ofmedical claims and litigation could single handedly justify the conversion to a
more friendly structure.
Based on these results, it was concluded thatCyclic Olefin copolymers provide new tools
for the design of flexible packaging in thepharmaceutical industry and beyond. COCs can
38
improve many of the properties of polyolefins. Among these are modulus, clarity, blocking,
sealing, andMVTR. Because of the enhancement in modulus, COCs offer significant
downsizing possibilities. Above all COC will not contribute to the destruction of the
environment while it enhances the company's image as leader that has emerged from the PVC
market. COC is an Olefin not like PVC it does not corrode the tooling, which would yield to
significant saving in constant tooling refinishing or replacement.
CONSIDERATIONS
Modification to the thermoformer to include static bars, ionized air, and/or grounding
devices to minimize static at the die cutting station might be required.
The PVC pricing is systematically coming down, which makes it difficult to justify
the project with no direct return on investment.
Changing from the current approved material would require new stability studies and
new submission to the FDA.
Currently, COC resin is only produced in one factory (Germany). If for any
unforeseen reason the production is disrupted, this could drastically affect the
production of the end user, which would in turn contribute toloss of market share.
39
REFERENCES
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Capus, J. M. (2001). Advancedmaterials andprocesses. AM&P, 159, 25.
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Draguta, V., Balaban, M., & Dimonie, AT. (1985). Olefin metathesis and ring-opening
polymerization ofcyclo-olefins(2nd
edition). New York: Wiley.
Encyclopedia Britannica (2004). Hermann Staudinger. Retrieved July 13, 2004, from Encyclopaedia
Britannica Online.
Environment Safety and Health Manual. (2004). Retrieved July 13, 2004 from
http://www.llnl.gov/es and h/hsm/doc 14.14/docl4-14.html
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Company Inc.
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Abstract 55,16005 (1961).
Imamolgu, Y., Zumreoglu-Karan, B., Amass, A.J. (Eds.). (1990). Olefin metathesis and polymerization
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cooperation
with the NATO Scientific Affairs Division.
Ivin, K.J. andMol, J.C. (1997). Olefinmetathesis andmetathesis
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Academic Press.
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http://www.mindbranch.com/aitaj^^
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Ozone Depletion Glossary. (2004). Retrieved July 13, 2004 from http://www.epa.gov/ozone/defns.html
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Selke, S. E. M. (1990). Packaging and the environment. Lancaster, PA: Technomic Publishing
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Seymour, R. B. (Ed.). (1982). History ofpolymer science and technology. New York: M.
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Titow,W.V. (1984). PVC technology(4th
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41
APPENDIX A: DEFINITIONS
Amorphous: Having no ordered arrangement. Polymers are amorphous when their chains are
tangled up in no specific arrangement. Polymers are not amorphous when their chains are lined
up in orderedcrystals.
Copolymer: A polymer made from more than one kind of monomer.
Crystal: A mass of molecules arranged in a neat and orderly fashion. In polymer crystal the
chains are lined up neatly. They are also bound together tightly by secondary interactions.
Glass transition temperature: The temperature at which a polymer changes from hard and
brittle to soft and pliable.
Hydrogen bond: A very strong attraction between a hydrogen atom which is attached to an
electronegative atom, and an electronegative atom which is usually on another molecule.For
example, the hydrogen atoms on one water molecule are very stronglyattracted to the oxygen
atoms on another water molecule.
8",H
8+0-
\ The hydrogenwith a partial positive
/
^charge is attracted to the oxygen with
0^ its partial negative charge.
H
Modulus: The ability of a sampleof a material to resist deformation. Modulus is usually
expressed as the ratio of stress exerted on thesample to the amount of deformation. For example,
tensile modulus is the ration of stress applied to the elongation,which results from the stress.
Monomer: A small molecule which may react chemicallyto link together with other molecules
of the same type to form a large molecule called apolymer.
OlefinMetathesis: A reaction between two molecules,both containing
carbon-carbon double
bonds. In olefin metathesis, the double bondcarbon atoms change partners,
to create two new
molecules, both containingcarbon-carbon double bonds.
RR'
>=<R
R'
R R R\R'
V../
A Ar: r
r* R"
r
RR"
42
Plasticizer: A small molecule that is added to polymer to lower its glass transition temperature.
Ring-opening polymerization: A polymerization in which cyclic monomer is converted into a
polymer, which does not contain rings. The monomer rings are opened up and stretched out inthe polymer chain, like this:
AB'
AAAAM j!^s
XB A>^J} MWNB A^
Strength: The amount of stress an object can receive before it breaks.
Thermoplastic: A material that can be molded and shaped when it's heated.
Thermal decomposition: A change that takes place in a material when you heat it or cool it,
such as melting, crystallization, or the glass transition.
Thermoset: A hard and stiff crosslinked material. Thermosets are different from thermoplastics,
which become moldable when heated. Thermosets are crosslinked, so they don't. Also, they are
different from crosslinked elastomers. Thermosets are stiff and don't stretch the way elastomers
do.
43